Menopausal syndrome consists of a number of varying and often highly distressing symptoms resulting from hormonal imbalance in the female body, specifically a deficiency of estrogen in the body. Symptoms of menopausal syndrome sufficiently severe to require treatment occur in approximately 50 percent of women. One particular symptom experienced by women is hot flashes or flushing. This is characterized by a sudden onset of warmth in the face and neck and often progressing to the chest. Such an episode generally lasts several minutes and is evidenced by a visible red flushing of the skin. Often such episodes are accompanied by sweating, dizziness, nausea, palpitations and diaphoresis.
In U.S. Pat. No. 5,789,443, granted on Aug. 4, 1998, the contents of which are expressly incorporated by reference as if fully set forth herein, the use of leucine either alone or in combination with other branched chain amino acids has been described for the treatment of flushing and the like associated with menopause.
Flushing, however, can be caused by other means than the reduction of estrogen resulting from the onset of natural or normal menopause. "Other means" refers to any causes of human flushing brought on by other than "normal" physical decreases in estrogen associated with normal or natural menopause. In other words, induced menopause can cause flushing. For example, flushing may be induced by certain drug administration. Drugs used to treat breast cancer, such as the anti-estrogens are known to induce flushing. Examples of the anti-estrogens include, but are not limited to, tamoxifen (1-p-.beta.-dimethylamino-ethoxypenyl-trans-1,2-dipheriyl-but-1-ene), and droloxifene ((E)-alpha-(para-(2-(Dimethylamino)ethoxy) phenyl)-alpha'-ethyl-3-s-tilbenol), faslodex (7.alpha.-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5(10)-tr iene-3-173-diol), and progestins such as, megestrol (17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione) and medroxyprogesterone ((6alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione). Another class of drugs used in the treatment of breast cancer is the aromatase inhibitors. Examples of the aromatase inhibitors include, but are not limited to, anastrazole (2,2[5-(1H-1,2,4-triazol-1-yl methyl)-1,3-phenylene]bis(2-methylpropiononitrile), fadrozole (4-(5,6,7,8-Tetrahydroimidazo(1,5-a)pyridin-5-yl)benzonitrile), letrozole (4-[1-(cyanophenyl)-1-(1,2,4-triazolyl)methyl]benzonitrile), vorzole (6-((4-chlorophenyl)-(1H-1,2,4-triazol-1-yl)methyl)-1-methyl-1H -benzotriazloe), aminoglutethimide(2-(p-aminophenyl)-2-ethyl -glutarimide), formestane (4-Hydroxyandrostenediona) and exermestane (6-Methyleneandrosta-1,4-diene-3,17-dione).
In the treatment of prostrate carcinoma, lutenizing hormone releasing hormone (LHRH) analogs are administered. Such endocrine therapy suppresses levels of testosterone and is known to cause flushing in about two thirds of the patients undergoing therapy. Examples of LHRH analogs include, but are not limited to, leuprolide acetate and goserelin acetate.
In the treatment of cancer, women subject to powerful drugs may cease menstruating and may experience flushing.
Flushing may be induced as a result of radiation therapy.
Flushing may also be induced by certain surgical procedures. Removal of the testes is known to induce flushing in about half the men receiving such a procedure. Removal of the ovaries is also known to induce flushing in women.